Respiratory hemoproteins such as myoglobin, hemoglobin, cytochrome, and hydroperoxidases, which are involved in oxygen transport and biological oxidation, will be modified by chemical exchange of the prosthetic groups and selective modification of the apoprotein moieties. The effects of such modification on the molecular structure and biochemical function of these hemoproteins, the electronic state of their prosthetic groups, and the model of their prosthetic group-apoprotein interaction will be characterized using various physical and chemical techniques, which include automatic oxygenation measurements, temperature-jump kinetics, optical spectroscopy, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), resonance Raman, and fluorescence spectroscopy in order to establish the correlation between molecular structure and biochemical function of these hemoproteins. The chemical modification technique will be further applied to hemoglobin to form hybrid hemoglobin tetramers containing different prosthetic groups in unlike subunits such as cobalt-iron hybrid hemoglobin and protohem-mesoheme hybrids in order to elucidate the molecular mechanism of subunit cooperativity and the mode of action of allosteric effectors such as 2,3-diphosphoglycerate (DPG) and inositol hexaphosphate. On the basis of knowledge and techniques acquired in this basic research, the chemical syntheses of artificial hemoproteins, particularly artificial hemoglobin which possesses more favorable functional properties for biomedical applications than the natural counterpart, will be attempted.